Journal
HUMAN MOLECULAR GENETICS
Volume 18, Issue 18, Pages 3516-3524Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddp296
Keywords
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Funding
- Netherlands Organization for Scientific Research (NWO) [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly [014-93-015, RIDE2]
- Netherlands Genomics Initiative (NGI)/NWO [050-060-810]
- Netherlands Forensic Institute
- NGI/NWO
- Erasmus University Medical Center
- Erasmus University Rotterdam
- Netherlands Organization for the Health Research and Development
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports of the Netherlands, the European Commission
- Municipality of Rotterdam
- NWO
- Erasmus MC
- Centre for Medical Systems Biology (CMSB)
- Ministry of Science, Economy and Transport of Schleswig-Holstein, Germany
- Swedish Research Council
- ALF
- Lundberg Foundation
- Torsten and Ragnar Soderberg's Foundation
- Novo Nordisk Foundation
- NWO: twin-family database for behavior genetics and genomic studies [480-04-004, 904-61-090, 904-61-193]
- Center for Medical Systems Biology
- Spinozapremie [56-464-14192]
- Centre for Neurogenomics and Cognitive Research (CNCR-VU)
- genome-wide analyses of European twin and population cohorts [EU/QLRT-2001-01254]
- Geestkracht program of ZonMW [10-000-1002]
- Genetic Association Information Network (GAIN)
- US National Institutes of Health
- GAIN
- NIMH [MH081802]
- Netherlands Genomics Initiative/Forensic Consortium Netherlands
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Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (P-combined = 3.4 x 10(-9)). Notably, a second SNP (rs6718438) located similar to 450 bp away and in strong LD (r(2) = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (P-combined = 2.1 x 10(-7)). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height.
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